Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
Browse
1 results
Search Results
Master Thesis Investigation of Biological Roles of Neuraminidase 3 and N-Acetylgalactosaminyltransferase Enzymes in Glycolipid Metabolism(Izmir Institute of Technology, 2020) Basırlı, Hatice Hande; Seyrantepe, VolkanGangliosides are sialic acid containing biomolecules and perform important functions by locating on cell membranes. Their catabolism regulated by sialidases while their synthesis was performed by glycosyltransferases. Neu3 reacts with gangliosides on plasma-membrane and acts in cellular processes. Neu3 mice model was studied without signs of altered brain activity and phenotypic alterations. In further studies, significance of Neu3 sialidase in bypass mechanism shown in Tay-Sachs disease mice model named as Hexa-/-Neu3-/- mice. Galgt enzyme produces 0-, a-, b-, and c-series of complex gangliosides. Galgt deficiency led to progressive axonal degeneration, decreased myelin volume, altered axo-glial junction integrity, male infertility and hindpaw-clasping in mice. However, the studies for showing In this study, we investigated altered ganglioside metabolism, ER-stress, oxidative stress, and apoptosis mechanisms in cortex, thalamus, and cerebellum tissues of 3- and 6-month-old Neu3-/-, Galgt-/-, and Neu3-/-Galgt-/- mice compared to age-matched WT control by performing molecular biological techniques (TLC, RT-PCR, and Western Blot analyses). Furthermore, we performed histopathologic and immunohistochemical analyses to examine the alterations in myelination, neuron number, and glyco-conjugate content, morphological abnormalities, and apoptosis in brain sections of single and double deficient mice models. We also performed behavioral assays like rotarod, passive avoidance and open field to show altered brain functions and behavioral abnormalities like anxiety, reduced motor balance, strength, and locomotory activity in addition to problems in memory formation. In line with these studies, we found that Neu3 and Galgt enzymes acts in the regulation of ganglioside metabolism in a region-specific and age-dependent manner.